Potassium Phosphate, Tribasic → N-[2-[[6-[[5-[5-fluoro-2-(acetoxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]amino]ethyl]prop-2-enamide

HRID 1774638Notes

Reaction equation

HRID 1774638 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[C:15]([NH:17][CH2:18][CH2:19][NH:20][C:21](=[O:24])[CH:22]=[CH2:23])[CH:14]=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:25]([O:28][CH2:29][C:30]1[C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][C:33]([F:45])=[CH:32][C:31]=1[N:46]1[C:58](=[O:59])[C:57]2[S:56][C:55]3[CH2:54][CH2:53][CH2:52][CH2:51][C:50]=3[C:49]=2[CH:48]=[N:47]1)(=[O:27])[CH3:26].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(#N)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:45][C:33]1[CH:32]=[C:31]([N:46]2[C:58](=[O:59])[C:57]3[S:56][C:55]4[CH2:54][CH2:53][CH2:52][CH2:51][C:50]=4[C:49]=3[CH:48]=[N:47]2)[C:30]([CH2:29][O:28][C:25](=[O:27])[CH3:26])=[C:35]([C:2]2[CH:3]=[C:4]([NH:10][C:11]3[N:16]=[C:15]([NH:17][CH2:18][CH2:19][NH:20][C:21](=[O:24])[CH:22]=[CH2:23])[CH:14]=[CH:13][CH:12]=3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)[CH:34]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 58043634(4-Fluoro-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetateHCID 118116339N-(2-(6-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-2-ylamino)ethyl)acrylamide

Product 1

HCID 118116546N-[2-[[6-[[5-[5-fluoro-2-(acetoxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]amino]ethyl]prop-2-enamideYield 31%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 105e (235 mg, 0.601 mmol), (4-fluoro-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-triene-5-yl}-6-(tetra-methyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetate 108c (299 mg, 0.601 mmol), Pd(dppf)Cl2(42.8 mg, 0.06 mmol) and K3PO4(382 mg, 1.80 mmol) in ACN (10 mL) and H2O (2 mL) was degassed and stirred at 85° C. for 4 h under nitrogen. The reaction mixture was concentrated and the residue was purified by silica gel chromatography (EA/PE=4/1) to give N-[2-[[6-[[5-[5-fluoro-2-(acetoxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]amino]ethyl]prop-2-enamide 105f (125 mg, 31%) as a brown solid. MS-ESI: [M+H]+ 684.3

Workup

  1. customwas degassed
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was purified by silica gel chromatography (EA/PE=4/1)

Sources & evidence

ORD record
ord-97c8daf41aa143ceb6eb6a5fafa89d2a
Source dataset
uspto-grants-2016_02
Patent number
US09260415B2

Reaction notes

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